Photo-antagonism of the GABAA receptor

Neurotransmitter receptor trafficking is fundamentally important for synaptic transmission and neural network activity. GABAA receptors and inhibitory synapses are vital components of brain function, yet much of our knowledge regarding receptor mobility and function at inhibitory synapses is derived...

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Main Authors:	Mortensen, Martin, Iqbal, Favaad, Pandurangan, Arun P., Hannan, Saad, Huckvale, Rosemary, Topf, Maya, Baker, James R., Smart, Trevor G.
Format:	Online
Language:	English
Published:	Nature Pub. Group 2014
Online Access:	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4124873/

id	pubmed-4124873
recordtype	oai_dc
spelling	pubmed-41248732014-08-14 Photo-antagonism of the GABAA receptor Mortensen, Martin Iqbal, Favaad Pandurangan, Arun P. Hannan, Saad Huckvale, Rosemary Topf, Maya Baker, James R. Smart, Trevor G. Article Neurotransmitter receptor trafficking is fundamentally important for synaptic transmission and neural network activity. GABAA receptors and inhibitory synapses are vital components of brain function, yet much of our knowledge regarding receptor mobility and function at inhibitory synapses is derived indirectly from using recombinant receptors, antibody-tagged native receptors and pharmacological treatments. Here we describe the use of a set of research tools that can irreversibly bind to and affect the function of recombinant and neuronal GABAA receptors following ultraviolet photoactivation. These compounds are based on the competitive antagonist gabazine and incorporate a variety of photoactive groups. By using site-directed mutagenesis and ligand-docking studies, they reveal new areas of the GABA binding site at the interface between receptor β and α subunits. These compounds enable the selected inactivation of native GABAA receptor populations providing new insight into the function of inhibitory synapses and extrasynaptic receptors in controlling neuronal excitation. Nature Pub. Group 2014-07-29 /pmc/articles/PMC4124873/ /pubmed/25072879 http://dx.doi.org/10.1038/ncomms5454 Text en Copyright © 2014, Nature Publishing Group, a division of Macmillan Publishers Limited. All Rights Reserved. http://creativecommons.org/licenses/by/4.0/ This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/
repository_type	Open Access Journal
institution_category	Foreign Institution
institution	US National Center for Biotechnology Information
building	NCBI PubMed
collection	Online Access
language	English
format	Online
author	Mortensen, Martin Iqbal, Favaad Pandurangan, Arun P. Hannan, Saad Huckvale, Rosemary Topf, Maya Baker, James R. Smart, Trevor G.
spellingShingle	Mortensen, Martin Iqbal, Favaad Pandurangan, Arun P. Hannan, Saad Huckvale, Rosemary Topf, Maya Baker, James R. Smart, Trevor G. Photo-antagonism of the GABAA receptor
author_facet	Mortensen, Martin Iqbal, Favaad Pandurangan, Arun P. Hannan, Saad Huckvale, Rosemary Topf, Maya Baker, James R. Smart, Trevor G.
author_sort	Mortensen, Martin
title	Photo-antagonism of the GABAA receptor
title_short	Photo-antagonism of the GABAA receptor
title_full	Photo-antagonism of the GABAA receptor
title_fullStr	Photo-antagonism of the GABAA receptor
title_full_unstemmed	Photo-antagonism of the GABAA receptor
title_sort	photo-antagonism of the gabaa receptor
description	Neurotransmitter receptor trafficking is fundamentally important for synaptic transmission and neural network activity. GABAA receptors and inhibitory synapses are vital components of brain function, yet much of our knowledge regarding receptor mobility and function at inhibitory synapses is derived indirectly from using recombinant receptors, antibody-tagged native receptors and pharmacological treatments. Here we describe the use of a set of research tools that can irreversibly bind to and affect the function of recombinant and neuronal GABAA receptors following ultraviolet photoactivation. These compounds are based on the competitive antagonist gabazine and incorporate a variety of photoactive groups. By using site-directed mutagenesis and ligand-docking studies, they reveal new areas of the GABA binding site at the interface between receptor β and α subunits. These compounds enable the selected inactivation of native GABAA receptor populations providing new insight into the function of inhibitory synapses and extrasynaptic receptors in controlling neuronal excitation.
publisher	Nature Pub. Group
publishDate	2014
url	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4124873/
_version_	1613121935056568320

Photo-antagonism of the GABAA receptor

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